Currently, biological agents are being used clinically to facilitate bone formation in bone grafting applications. Among the more common agents are demineralized bone matrix (DBM), bone marrow aspirate (BMA), and recombinant human bone morphogenetic proteins (BMP). Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in combination with an Absorbable Collagen Sponge (“ACS”); (Integra LifeSciences Corporation, Plainsboro, N.J.) has been shown to induce bone formation in various clinical (Boden S. D., 24 Orthop Nurs, 49 (2005); Burkus J. K., et al, 15 J Spinal Disorders, 337 (2002); Govender S., et al, 84-A J Bone Joint Surg., 2123 (2002); Khan S. N., et al, 4 Expert Opin Biol Ther., 741 (2004); Haid R. W., et al, 4 The Spine Journal, 527 (2004); Sandhu H. S., et al, 28 Spine, S85 (2003); Termaat M. F., et al, 87 Surg., 1367 (2005) and animal models (Akamaru T., et al: 28 Spine, 429(2003); Sandhu H. S., et al, 27 Spine, 567 (2002); Sandhu H. S., et al, 22 Spine, 1171 (1997)).
The rhBMP-2/ACS combination implant and the INFUSE® Bone Graft (Medtronic Sofamor Danek, Memphis, Tenn.), have been used as autograft replacement for lumbar spinal fusions, and subsequently approved for acute tibial fractures in 2004. (Termaat M. F., et al, 87 Surg., 1367 (2005)). Autograft and many of the bone graft substitutes are radiopaque allowing surgeons to visualize the graft material placement using fluoroscopy or plain radiographs. INFUSE® Bone Graft is radiolucent and thus cannot be seen radiographically after implantation. (Burkus J. K., et al, 28 Spine, 372 (2003)). For surgeons used to working with metal implants, the sudden loss of verifying the implant placement on radiographs is a concern. There have been many inquiries into using radiopaque media in combination with INFUSE® Bone Graft. The concern however, with mixing these products is inactivating the rhBMP-2 that has been clinically shown to be equivalent to iliac crest autograft.
In view of the above considerations, it is clear that there is a need for an intraoperative radiographically visible product to supplement existing methods of implanting medical devices within a patient's body.